Copper-Catalyzed Alkynylation of -Generated Azoalkenes: An Umpolung Approach to Pyrazoles.

A straightforward umpolung approach to regioselectively N-protected polysubstituted pyrazoles starting from aromatic α-halohydrazones and terminal alkynes has been developed. In this process, azoalkenes generated from α-halohydrazones are involved in the Cu(I)-catalyzed Michael addition with alkynes to give α-alkynyl-substituted hydrazones that cyclize to give the target pyrazoles in 37-85% yield. The method employs readily available starting materials and features good functional group compatibility (nitro, sulfonyl, cyano, trimethylsilyl, and primary bromoalkyl groups, esters, and alcohols are tolerated) and scalability.

Michael addition of -nucleophiles to azoalkenes provides simple access to phosphine oxides bearing an alkylhydrazone moiety.

β-Hydrazonophosphine oxides are precursors of useful organophosphorus compounds, including phosphorylated -heterocycles, α-aminophosphonates, and vinylphosphonates. In this work, a general transition metal-free synthesis of β-hydrazonophosphine oxides was developed. The method relies on the Michael addition of phosphine oxides RP(O)H to reactive azoalkenes (1,2-diaza-1,3-butadienes), which are generated from α-halohydrazones and Hunig's base.

Nucleophilic Halogenation of Cyclic Nitronates: A General Access to 3-Halo-1,2-Oxazines.

In this article, comprehensive studies on the nucleophilic chlorination and bromination of readily available six-membered cyclic nitronates (1,2-oxazine--oxides) are reported. Under optimized conditions (POCl or (COBr) with Hünig's base), 3-halo-substituted 1,2-oxazines, which are difficult to access by other routes, were obtained in good to high yields. The latter were shown to be convenient precursors to other 3-substituted 1,2-oxazine derivatives using Lewis/Brønsted acid-assisted substitution of the halide atom for C-, S-, and N-nucleophiles.

Acylation of Nitronates: [3,3]-Sigmatropic Rearrangement of in Situ Generated N-Acyloxy, N-oxyenamines.

Acylation of nitronates affords α-acyloxyoxime derivatives via an umpolung functionalization of the α-position. This transformation involves generation of hitherto unknown N-acyloxy, N-oxyenamines and their fast [3,3]-sigmatropic rearrangement driven by the cleavage of the weak N-O bond. The reaction has a broad scope, and it is regioselective in the case of nitronates possessing nonsymmetrically substituted α-positions.

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia.

Exhaustive Michael-type alkylations of amines and ammonia with azoalkenes (generated from α-halohydrazones) were demonstrated as an efficient approach to poly(hydrazonomethyl)amines - a novel class of polynitrogen ligands. An intramolecular cyclotrimerization of C=N bonds in tris(hydrazonomethyl)amine to the respective 1,4,6,10-tetraazaadamantane derivative was demonstrated.